PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).

METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable.

RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively).

CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.


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Cite as

Arabi, Y., Gordon, A., Derde, L., Nichol, A., Murthy, S., Al-Beidh, F., Annane, D., Al-Swaidan, L., Beane, A., Beasley, R., Berry, L., Bhimani, Z., Bonten, M., Bradbury, C., Brunkhorst, F., Buxton, M., Buzgau, A., Cheng, A., de Jong, M., Detry, M., Duffy, E., Estcourt, L., Fitzgerald, M., Fowler, R., Girard, T., Goligher, E., Goossens, H., Haniffa, R., Higgins, A., Hills, T., Horvat, C., Huang, D., King, A., Lamontagne, F., Lawler, P., Lewis, R., Linstrum, K., Litton, E., Lorenzi, E., Malakouti, S., McAuley, D., McGlothlin, A., Mcguinness, S., McVerry, B., Montgomery, S., Morpeth, S., Mouncey, P., Orr, K., Parke, R., Parker, J., Patanwala, A., Rowan, K., Santos, M., Saunders, C., Seymour, C., Shankar-Hari, M., Tong, S., Turgeon, A., Turner, A., Van de Veerdonk, F., Zarychanski, R., Green, C., Berry, S., Marshall, J., McArthur, C., Angus, D., Webb, S. & REMAP-CAP Investigators 2021, 'Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial', Intensive Care Medicine, 47 (8 ), pp. 867-886 . https://doi.org/10.1007/s00134-021-06448-5

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Last updated: 15 July 2023
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